We propose to test the novel hypothesis that a persistent history of psychiatric disorder might accelerate individuals'risk of progression toward age-related disease. Specifically, the hypothesis is that people who suffer chronic or recurrent psychiatric disorders during early adulthood will, already by age 38, show cognitive decline and abnormal status on sub-clinical biomarkers that are known to be prognostic early warning signs for late-life diseases, frailty and disability. Rather than focus on psychiatric disorders as an outcome, we study psychiatric disorders as a potentially preventable `exposure'that may accelerate aging. METHOD: We will test this hypothesis in the context of the Dunedin Study, a longitudinal study from birth to age 38 of a representative birth cohort of men and women (N=1037). A unique design feature is that baseline physical health and baseline neuropsychological assessments were carried out from birth to age 13, prior to the onset of most psychiatric disorders. To our knowledge, no other study of the health consequences of psychiatric disorder has these prospective baseline data, which are essential to test whether health and neuropsychological functions have deteriorated in individuals with persistent psychiatric disorder. Cohort members'psychiatric histories of recurrent Depression, recurrent Anxiety, chronic Schizophrenia-syndrome, persistent Alcohol Dependence, and persistent Cannabis Dependence will be defined using data from repeated assessments across 20 intervening years in this longitudinal study. Here we propose to assess the cohort again at age 38, for new data collection. We will assess sensitive outcome measures of sub-clinical health status that are known predictors of age-related diseases in later life: neuropsychological tests of memory and executive functions, the metabolic syndrome, immunological biomarkers, and shortened telomere length. These markers were chosen because they show meaningful variation among people in their late 30's and are known early warning signs for dementia, cardiovascular disease and diabetes. INNOVATION AND SIGNIFICANCE: Life expectancy is growing longer and longer. Policy makers and citizens are concerned that our extra years of life should be healthy, productive, and enjoyable, not extra years of disease and disability. The hope of preventing age-related diseases and of increasing health expectancy requires research to identify candidate risk targets that can be treated successfully, in early- to-middle adulthood. If the hypothesis that psychiatric disorder accelerates the sub-clinical progression toward age-related disease were shown to be true by our proposed research, this would imply that age- related disease could be reduced by successfully treating psychiatric disorders early in life. PUBLIC HEALTH RELEVANCE: As life expectancy grows longer and longer, policy makers and citizens are concerned that our extra years should be healthy, productive, and enjoyable, not extra years of disease and disability. The hope of preventing age-related diseases requires research to identify candidate risk targets that can be treated successfully, in early-to-middle adulthood, before the onset of age-related disease. If the hypothesis that psychiatric disorder accelerates the sub-clinical progression toward age-related disease were shown to be true by our proposed research, this would imply that age-related diseases could be reduced by successfully treating psychiatric disorders early in life.